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DNA 'library' The clearest picture yet of how our genes are regulated to make the body work has been unveiled in a major international study.

The scientists, including Australians, have mapped how a network of switches, built into human DNA, controls where and when genes are turned on and off.

These "maps", published today in two major studies in Nature, significantly increase our understanding of the human genome, which contains the genetic instructions needed to build and maintain all the many different cell types in the body.

The three-year-long project, called FANTOM5 (Functional Annotation of the Mammalian genome) and led by the RIKEN Centre for Life Science Technologies in Japan, involved more than 250 scientists across 20 countries and regions, including Australia.

"This beautiful diversity of cell types allow us to see, think, hear, move and fight infection - yet all of this is encoded in the same genome."

All of our cells contain the same instructions, but genes are turned on and off at different times in different cells.

This process is controlled by switches - called promoters and enhancers - found within the genome. It is the flicking of these switches that makes a muscle cell different to a liver or skin cell.

The FANTOM5 team studied the largest yet set of cell types and tissues from humans and mice so they could identify the location of these switches within the genome.

They also mapped where and when the switches are active in different cell types and how they interact with each other.

Professor David Hume, director of the Roslin Institute at Britain's Edinburgh University and one of the lead researchers on the project, uses the analogy of an aeroplane: "We have made a leap in understanding the function of all of the parts. And we have gone well beyond that - to understanding how they are connected and control the structures that enable flight."

'Intricate'

Associate Professor Ernst Wolvetang, also at the Australian Institute of Bioengineering and Nanotechnology at the University of Queensland, says the work is a game changer in the field.

As part of the same project, Wolvetang and his team have been able to look at brain stem cells and see how "intricate and complex" the gene regulatory networks are already at that basic level of development.

"It is an amazing compendium of information," he says.

"Nobody up to date has taken so many cell lines and worked out which genes are on and which genes are off - and in this case we now know the whole story."

Wolvetang says the "map" will be a major resource for researchers and already researchers are investigating how to turn one cell type into another.

Researchers also hope the FANTOM5 work will be a reference atlas to figure out which genes are involved, and how, in a whole range of diseases.

In a linked study, a Roslin Institute team used information from the atlas to investigate the regulation of an important set of genes required to build muscle and bone.

Another study used the FANTOM5 atlas to look at the regulation of genes in cells of the blood, producing what scientists described as a roadmap of blood cells that will help them pinpoint where and how cancerous tumours start to grow.

"Now that we have these incredibly detailed pictures of each of these cell types, we can now work backwards to compare cancer cells to the cells they came from originally to better understand what may have triggered the cells to malfunction, so we will be better equipped to develop new and more effective therapies," says Forrest.